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Sunday, 5 April 2009

Evolutionary Medicine (3)

This is the third installment. Click here to go the first one, and here for the second one.

The fact that our bodies may be largely bundles of compromises is also counter-intuitive.Of course, we’re already a little familiar with the idea: the sickle cell allele is a special kind of trade-off, whereby the best option for evolution in some parts of the world is a partial deficiency! Ageing is perhaps the biggest compromise at all, according to the leading theory of senescence. The first step in understanding why we age is to distinguish between wear-and-tear and senescence.Obviously all things are subject to attrition, but the crucial question is not why this is so, but why this isn’t repaired or overcome.The question isn’t why our molars wear down with age, but why they aren’t replaced.The question isn’t why my bones will lose calcium from today until the day I die, but why I can’t lay it down at a matching rate.And agelessness isn’t some hopeless dream; it’s amply displayed in cancer cell lines grown around the world, which show no senescence at all.Why aren’t we like that?

Geneticists had long-since noted an interesting fact: the selection pressure on a gene (either positive or negative) necessarily decreases with age, and that is because even without ageing, we wouldn’t be immortal.Sooner or later, a lightening bolt, a fall, a rival or (more likely) a microbe would get us, and so theoretical immortality would never translate into actual immortality.To use an extreme example, therefore, a gene that had an effect at age 999 would not often have the chance to express itself, and so would practically have no selection pressure acting upon it, either positively or negatively.

Williams took this idea to the next level with his brilliant theory of “antagonistic pleitropy”. He first noted that most genes are pleiotropic; that is, they have more than one effect.He then surmised that pleiotropic genes in which positive effects occurred earlier on in life than their negative effects could be selected for - even if their positive traits were outweighed by their negative ones.This is because genes with effects towards the beginning of life would be weighted and counted as more significant, since they were under maximum selection pressure.The result, said Williams (and most researchers since) is ageing.

A vivid example from his original paper is that of a hypothetical gene that increased calcium deposition in the bones, but also gradually in the coronary arteries.Even though enough calcium deposition in the coronary arteries would inevitably be fatal eventually, the selection pressure against this effect would be weak, since it happened late in life when many people would have died from other causes.It is conceivable that such a gene would be selected for since the strong selection pressure towards stronger bones would ‘outvote’ the weaker selection pressure against coronary artery disease.

Such compromises are likely to be legion, as Stephen Pinker notes.“Some materials might be strong and light but wear out quickly, whereas others might be heavier but more durable.Some biochemical processes might deliver excellent products but leave a legacy of accumulating pollution within the body.There might be a metabolically expensive cellular repair mechanism that comes in most useful late in life when wear and tear have accumulated.”All things being equal, evolution will inevitably tend to favour things with benefits to young people and costs to old people, over things with a more equal spread.Note that this is a good example of an ultimate explanation, and so lends neither support nor criticism to other possible proximate explanations, like the free-radical theory of ageing.Let’s assume that free radical damage does account for most of ageing.The broader questions would still need answering, for instance “Why don’t we have better antioxidant mechanisms?”, or “Why can’t we better repair or replace the damage caused by free radicals?”

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This is a site dedicated to interesting and sometimes complicated ideas - in the abstract. This is NOT a site from which to obtain medical advice for yourself, your family or your friends. When it comes to specific health problems, nothing can replace the dedicated attentions of a medical doctor.